Genome-Wide Association Study of Panic Disorder

• Published in: EUROPEAN NEUROPSYCHOPHARMACOLOGY 2019, Vol.29, p.S776-S776
• Main Authors: Forstner, Andreas J., Awasthi, Swapnil, Wolf, Christiane, Maron, Eduard, Erhardt, Angelika, Eriksson, Elias, Lavebratt, Catharina, Allgulander, Christer, Woldbye, David P.D., Mors, Ole, Binder, Elisabeth B., Rück, Christian, Ripke, Stephan, Deckert, Jürgen, Schumacher, Johannes
• Format: Article
• Language: English
• Subjects: Medicin och hälsovetenskap
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2017.06.144

Panic Disorder (PD) is one of the most common anxiety disorders with a lifetime prevalence of about 4%. The disorder is characterized by recurrent episodes of abrupt intense fear accompanied by additional physiological or cognitive symptoms. Although PD shows moderate heritability estimates of 30-54%, the genetic variants contributing to PD are largely unknown, with only few and inconsistent loci reported to date. To address the challenge of underpowered individual studies, we conducted the largest genome-wide association study of PD to date comprising more than 9,900 individuals. In our study, we generated genome-wide SNP data from 2,147 clinically well-characterized patients with PD and 7,760 ethnically matched controls. The samples originate from four different European countries (Denmark, Estonia, Germany and Sweden). Standard GWAS quality control procedures were performed on each dataset individually. Imputation was performed using the 1000 Genomes Project reference panel. Then a meta-analysis was performed using the Ricopili pipeline (https://sites.google.com/a/broadinstitute.org/ricopili/). In our meta-analysis, we did not identify any genome-wide significant locus. 36 linkage disequilibrium independent SNPs had a p-value < 1e-05. Leave-one-out analyses demonstrated highly significant polygenetic risk scores with an explained variance of up to 3%. Using the recently published LD Score regression method on our GWAS data the estimated heritability for PD was 0.2923. In this collaborative study with sample sizes being larger than any other PD GWAS published to date, we did not identify any genome-wide significant locus. However, our PD meta-analysis shows highly similar characteristics as similar sized GWAS previously conducted in schizophrenia. LD Score regression analysis provides the first SNP-based heritability estimate for PD based on genotype data of more than 9,900 individuals. Replication of our top findings in independent European datasets as well as further pathway analyses are currently underway and will be presented.